依布硒啉治疗耐药细菌感染的研究进展

Research in the treatment of drug-resistant organisms infections with Ebselen

多重耐药菌(MDRO)感染性疾病数量逐步上升,对之有效的抗菌药物相对较少,尤其全耐药肺炎双球菌、耐碳青霉烯类细菌等超级细菌的出现,使临床陷入了无药可用的窘境。现研究表明单独使用依布硒啉能调控MDRO中硫氧还蛋白还原酶(TrxR),使硫氧还蛋白(Trx)活性下降,依布硒啉联合银能降低谷胱甘肽(GSH)体系活性,阻碍线粒体中呼吸链上电子传递,降低细菌抗活性氧(ROS)能力、减少ATP产生,影响其氧化蛋白的修复和翻译后修饰,导致MDRO体内ROS增加,并抑制细菌DNA合成,起到双重杀菌作用。本文对依布硒啉治疗MDRO感染的研究进展进行综述。

The number of infectious diseases caused by multidrug resistant organisms(MDRO)is gradually increasing,and there are relatively few effective antimicrobials against them.Especially,the emergence of superbacteria such as all drug-resistant Diplococcus pneumoniae,carbapenem-resistant bacteria and other superbacteria has put the clinic into a dilemma of no drugs available.The current research shows that the use of ebselen alone can regulate the thioredoxin reductase(TrxR)in MDRO,reducing the activity of thioredoxin(Trx).The combination of ebselen and silver can reduce the activity of glutathione system,hinder the electron transfer on the respiratory chain in mitochondria,reduce the ability of bacteria to resist reactive oxygen species(ROS),reduce ATP production,affect the repair of its oxidized protein and Post-translational modification,lead to the increase of ROS in MDRO,and inhibit bacterial DNA synthesis,playing a dual bactericidal role.This article reviews the research progress of ebselen in the treatment of MDRO infection.